In previous work, mouse lines were selected for resistance (R) or for susceptibility (S) to fescue toxicosis based upon reductions in post-weaning growth rate caused by an endophyte-infected diet. The first objective of the current experiment was to determine whether long term reproduction of S mice was more severely depressed than that of R mice by the toxic diet. The second objective was to quantify glutathione-S-epoxytransferase (GST) and uridine diphosphate glucuronosyl-transferase (UDPGT) activities in R and S dams form the experiment and to determine whether reproduction during continuous cohabitation and liver detoxification enzyme activities were correlated within line x diet groups. Effects of the toxic diet were detectable within the first litters produced. Reproduction was more seriously influenced by the toxic diet within the S line than within the R line when these measures were compared within four equal time phases. The effects of the toxic diet on reproduction were greatest early in the experiment; by the fourth time phase differences among line x diet groups, with the exception of litter weight, were not significant. Percentage differences in total reproduction were greater between S mice fed the non-toxic diet and S mice fed the toxic diet than those between the R mice fed the non-toxic and toxic diets. Averaged across diets, GST activities were higher in R mice, but UDPGT activities were not significant. Within R line mice, GST was correlated with three reproductive measures, but UDPGT activity was not correlated with reproduction within any line x diet group.